JP5630998B2 - 機能的粒子のためのポリマー - Google Patents
機能的粒子のためのポリマー Download PDFInfo
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- JP5630998B2 JP5630998B2 JP2009511056A JP2009511056A JP5630998B2 JP 5630998 B2 JP5630998 B2 JP 5630998B2 JP 2009511056 A JP2009511056 A JP 2009511056A JP 2009511056 A JP2009511056 A JP 2009511056A JP 5630998 B2 JP5630998 B2 JP 5630998B2
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- A61K47/6935—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being obtained otherwise than by reactions involving carbon to carbon unsaturated bonds, e.g. polyesters, polyamides or polyglycerol
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- A61K9/513—Organic macromolecular compounds; Dendrimers
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Description
本発明の種々の局面に至る研究は、少なくとも一部、国立癌研究所、認可番号第CA119349、および国立生物医学画像・生物工学研究所、認可番号第EB003647によって後援された。米国政府は、本発明において特定の権利を有し得る。
本出願は、2006年5月15日に出願され、「機能的粒子の開発のための複数ブロックコポリマー」と題する、本明細書中に参考として援用される、Farokhzadらによる米国仮特許出願第60/747,240号の利益を主張している。
本発明は一般に、ポリマーおよびマクロ分子に、そして特にナノ粒子のような粒子において有用なプロックポリマーに関する。
活性成分の制御された放出をともなう患者への薬物の送達は、数十年の間、研究の活発な領域であり、ポリマー科学における多くの最近の発展、ならびに核酸、タンパク質、およびペプチドのような、より不安定な薬学的薬剤を送達する必要性によって活気づけられた。さらに、制御放出ポリマーシステムは、その他の薬物送達方法より長い時間の期間に亘って最適範囲にある薬物レベルを提供するように設計され得、それ故、薬物の効き目を増加し、そして患者コンプライアンスに付随する問題を最小にする。
(項目1)
組成物であって:
約1マイクロメーターより小さい平均特徴寸法を有する粒子を含み、該粒子が、生体適合性ポリマーを含む第1の部分、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含む第2の部分を含むマクロ分子を含み、該成分が、該粒子の内部で本質的にゼロでない濃度を有する、組成物。
(項目2)
上記成分が、少なくとも約1000Daの分子量を有する、項目1に記載の組成物。
(項目3)
上記成分が、約1000Daを超えない分子量を有する、項目1に記載の組成物。
(項目4)
上記マクロ分子が、ブロックコポリマーである、項目1に記載の組成物。
(項目5)
上記マクロ分子が、両親媒性である、項目1に記載の組成物。
(項目6)
上記マクロ分子の少なくとも一部分が、生分解性である、項目1に記載の組成物。
(項目7)
上記マクロ分子の少なくとも一部分が、加水分解可能である、項目1に記載の組成物。
(項目8)
上記生体適合性ポリマーが、ポリ(ラクチド−コ−グリコリド)を含む、項目1に記載の組成物。
(項目9)
上記標的化成分が、ポリペプチドを含む、項目1に記載の組成物。
(項目10)
上記標的化成分が、アプタマーを含む、項目1に記載の組成物。
(項目11)
上記標的化成分が、前立腺特異的膜抗原に特異的に結合する、項目1に記載の組成物。
(項目12)
上記標的化成分が、抗体または抗体フラグメントを含む、項目1に記載の組成物。
(項目13)
上記標的化成分が、細胞表面レセプターに特異的に結合する、項目1に記載の組成物。
(項目14)
上記標的化成分が、生物学的実体に特異的に結合する、項目1に記載の組成物。
(項目15)
上記粒子が、上記生体適合性ポリマーを含み、そして上記成分を含まない第2のマクロ分子をさらに含む、項目1に記載の組成物。
(項目16)
上記粒子が、薬物をさらに含む、項目1に記載の組成物。
(項目17)
上記薬物が、疎水性である、項目16に記載の組成物。
(項目18)
上記粒子が、核酸を含む、項目1に記載の組成物。
(項目19)
上記粒子が、ペプチドまたはタンパク質を含む、項目1に記載の組成物。
(項目20)
上記粒子が、ドセタキセルを含む、項目1に記載の組成物。
(項目21)
上記粒子が、酵素を含む、項目1に記載の組成物。
(項目22)
上記粒子が、約150nmより小さい平均特徴寸法を有する、項目1に記載の組成物。
(項目23)
上記ブロックコポリマーが、ポリ(アルキレングリコール)を含む第3のブロックをさらに含む、項目1に記載の組成物。
(項目24)
上記ポリ(アルキレングリコール)が、ポリ(エチレングリコール)を含む、項目23に記載の組成物。
(項目25)
上記粒子が:
上記マクロ分子を含む溶液を提供する工程;および
該粒子を生成するために該溶液をポリマー非溶媒と接触する工程、を包含するプロセスによって作製される、項目1に記載の組成物。
(項目26)
上記マクロ分子を含む溶液が有機溶媒であり、そして上記ポリマー非溶媒が水溶液である、項目25に記載の組成物。
(項目27)
所望の性質を備えたナノ粒子を作り上げる方法であって:
第1の生体適合性ポリマー、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含む第1のマクロ分子を提供する工程;
第2の生体適合性ポリマーを含む第2のマクロ分子を提供する工程;
該第1のマクロ分子および該第2のマクロ分子を異なる比で含む混合物からナノ粒子を形成することにより、該第1のマクロ分子および該第2のマクロ分子の異なる比を有するナノ粒子のライブラリーを生成する工程;および
1つ以上の所望の性質を有するナノ粒子の該ライブラリーからナノ粒子を識別する工程、を包含する、方法。
(項目28)
上記第1の生体適合性ポリマーが、上記第2の生体適合性ポリマーと実質的に同じである、項目27に記載の方法。
(項目29)
上記第1のポリマーが、ポリ(エチレングリコール)をさらに含む、項目27に記載の方法。
(項目30)
上記第2のポリマーが、ポリ(エチレングリコール)をさらに含む、項目27に記載の方法。
(項目31)
上記第1の生体適合性ポリマーが、ポリ(ラクチド−コ−グリコリド)を含む、項目27に記載の方法。
(項目32)
上記ナノ粒子を形成することの前に、薬物を添加することをさらに包含する、項目27に記載の方法。
(項目33)
上記薬物が、ドクリタキセルである、項目32に記載の方法。
(項目34)
上記ナノ粒子を形成することの前に、干渉RNAを添加することをさらに包含する、項目27に記載の方法。
(項目35)
上記ナノ粒子を形成することの前に、ペプチドまたはタンパク質を添加することをさらに包含する、項目27に記載の方法。
(項目36)
上記ナノ粒子を形成することの前に、酵素を添加することをさらに包含する、項目27に記載の方法。
(項目37)
ライブラリーを生成する方法であって:
繰り返しユニットを有する第1のブロック、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含む第2のブロックを含む第1のマクロ分子を提供する工程;
第1の繰り返し単位を含むが、該標的化成分を含まない第2のポリマーを提供する工程;および
該第1のマクロ分子および該第2のポリマーを異なる比で含む混合物からナノ粒子を形成することにより、該第1のマクロ分子と該第2のポリマーの異なる比を有するナノ粒子のライブラリーを生成する工程、を包含する、方法。
(項目38)
組成物であって:
約1マイクロメーターより小さい平均特徴寸法を有する粒子であって、第1のマクロ分子および第2のマクロ分子を含む粒子を含み;
ここで、該第1のマクロ分子が、第1の生体適合性ポリマー、ポリ(アルキレングリコール)、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含むブロックコポリマーであり;
そしてここで、該第2のマクロ分子が、ポリ(アルキレングリコール)および該第1の生体適合性ポリマーから区別可能な第2の生体適合性ポリマーを含むブロックコポリマーである、組成物。
(項目39)
組成物であって:
約1マイクロメーターより小さい平均特徴寸法を有する粒子であって、第1のマクロ分子および第2のマクロ分子を含む表面を有する粒子を含み、該第1のマクロ分子が、第1の長さを有する第1のポリ(アルキレングリコール)鎖、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含み、そして該第2のマクロ分子が、該第1の長さとは異なる第2長さを有するポリ(アルキレングリコール)鎖を含む、組成物。
(発明の要旨)
本発明は、一般に、ポリマーおよびマクロ分子に関し、そして特に、ナノ粒子のような粒子において有用なブロックポリマーに関する。本発明の主題は、いくつかの場合、相互関連する産物、特定の問題に対する代替えの解決、および/または1つ以上のシステムおよび/または物品の複数の異なる使用を含む。
本発明は、一般に、ポリマーおよびマクロ分子に、特に、ナノ粒子のような粒子で有用なブロックポリマーに関する。本発明の1つの局面は、所望の性質を備えるナノ粒子を作り上げる方法に関する。1つのセットの実施形態では、この方法は、2つ以上のマクロ分子を異なる比で一緒に混合することにより形成され得る、高度に制御された性質を有するナノ粒子のライブラリーを生成することを含む。1つ以上のマクロ分子は、生体適合性ポリマーへの成分のポリマー結合体であり得る。いくつかの場合には、このナノ粒子は、薬物を含み得る。上記成分は、いくつかの実施形態では、約1000Daより大きい分子量を有し得;例えば、上記成分は、アプタマーのようなポリペプチドまたはポリヌクレオチドを含み得る。上記成分はまた、標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分であり得る。本発明の別の局面は、このようなポリマー結合体を生成するシステムおよび方法に関する。いくつかの実施形態では、ポリマーを含む溶液が、不混和液体のような液体と接触され、上記ポリマー結合体を含むナノ粒子を形成する。本発明のその他の局面は、このようなライブラリーを用いる方法、このようなポリマー結合体を用いるか、または投与する方法、このようなポリマー結合体の使用を促進する方法、このようなポリマー結合体を含むキットなどに関する。
GGGAGGACGAUGCGGAUCAGCCAUGUUUACGUCACUCCUUGUCAAUCCUCAUCGGC(配列番号1)を有する。
トリウム、テガファー、テルラピリリウム、テロメラーゼインヒビター、テロキサントロンハイドロクロライド、テモポルフィン、テモゾロミド、テニポシド、テロキシロン、テストラクトン、テトラクロロロデカノキシド、テトラゾミン、タリブラスチン、タリドミド、モアミプリン、チオコラリン、チオグアニン、チオテパ、トロンボポイエチン、トロンボポイエチン模倣物、サイマルファシン、トロンボポイエチンレセプターアゴニスト、トモトリナン、甲状腺刺激ホルモン、チアゾフリン、錫エチルエピオプルプリン、チラパザミン、チタノセンジクロライド、トポテカンハイドロクロライド、トプセンチン、トレミフェン、トレミフェンシトレート、全能幹細胞因子、翻訳インヒビター、トレストロンアセテート、トレチノイン、トリアセチルウリジン、トリシリビン、リン酸トリシリリビン、トリメトレキセート、トリメトレキセートグルクロネート、トリプトレリン、トロピセトロン、チュブロゾールハイドロクライド、チュロステリド、チロシンキナーゼインヒビター、チフォスチン、UBCインヒビター、ウベニメックス、ウラシルマスタード、ウレデパ、泌尿生殖器洞由来成長阻害因子、ウロキナーゼレセプターアンタゴニスト、バプレオチド、バリオリンB、ベラレゾール、ベラミン、ベルディン、ベルテポルフィン、ビンブラスチンサルフェート、ビンクリスチンサルフェート、ビンデスチン、ビンデスチンサルフェート、ビネピディンサルフェート、ビングリシネートサルフェート、ビンロイロシンサルフェート、ビノレルビンタートレート、ビンロシディンサルフェート、ビンキサルチン、ビンゾリディンサルフェート、ビタキシン、ボロゾール、ザノテロン、ゼニプラチン、ゼラスコルブ、ジノスタチン、ジノスタチンスティマラマー、またはゾルビシンハイドロクロライドのような抗癌薬剤であり得る。
この実施例は、本発明の1つの実施形態による3ブロックポリマーのポリマー合成を示す。カルボキシ末端改変高分子量PLGA(HFIP、ヘキサフルオロ−2−プロパノール中0.6dL/gの固有粘度をもつ)は、Absorbable Polymers Internationalから購入した。二官能性PEG(NH2−PEG−COOH)は、Nektar Therapeuticsから購入した。アミン改変PSMAアプタマーは、RNA−TecNV(Leuven、Belgium)から購入した。すべてのその他の試薬は、Sigma Aldrichから購入した。
この実施例は、標的化特定細胞、身体の組織、または器官のような適用のため;そして複数ブロックコポリマーの一部であり得る粒子表面上の「ステルス」材料の存在によって宿主免疫原性を最小にする能力を有し得;そして持続された速度で薬学的薬物を放出する能力を有し得る、所定の官能化表面を有する小スケール粒子(すなわち、ピコ、ナノまたはマイクロ粒子)を作り上げるための複数ブロックポリマーの合成を示す。これらの小粒子は、研究ツールとして、または診断、治療、または診断および治療適用の組み合わせのために特定細胞、組織、または器官を標的にするための臨床用途のための有用性を有し得る。この実施例はまた、ナノ粒子形成の前に、生体マクロ分子ブロックによるポリマーの予備官能化を示す。
この実施例は、ナノ粒子表面上で発現されるアプタマーの量の決定を示す。ナノ粒子表面上で異なるリガンド密度を含むナノ粒子のライブラリーが、実施例1のアプタマーPEG−PLGAの3ブロックを、2ブロック溶液で希釈することにより処方され得ることが示すために、この3ブロックコポリマーは、PLGA−PEGの2ブロックコポリマー中で系列的に希釈され、そして水中で沈殿させた。ナノ粒子表面上のA10アプタマーリガンド密度を定量化するために、ナノ粒子表面上に残るA10アプタマーとPEGのカルボキシ官能基との間のアミド結合が塩基で加水分解され、そして回収されたRNAアプタマーの量が分光光度計により定量化された。ナノ粒子処方物中のアプタマー3ブロックを増加することは、ナノ粒子表面から回収されるアプタマーの量を直線的に増加したことが見出された。例えば、2ブロックに対するアプタマー3ブロックの比を0.02〜0.10に増加することは、ナノ粒子表面上のアプタマーの量を、100マイクログラムから450マイクログラムまで増加した。ナノ粒子表面から回収されたアプタマーリガンドの量を、NP処方物中に存在するアプタマーの量と比較することにより、アプタマー3ブロック処方物を増加することは、NP表面上で発現され得るアプタマーの合計比率を増加することが見出された。図9Aおよび9Bをインビトロおよびインビボ摂取研究と組み合わせることにより、リガンド表面密度の量が、所望の治療適用のために正確に制御され得る。例えば、インビトロナノ粒子摂取研究およびインビボ研究に基づき、2%の3ブロック処方物が、最小量の非特異的取り込みでLNCap前立腺癌腫瘍を標的にするに十分であったことが見出された。図9Aおよび9Bを用い、2%処方物中で約50%のアプタマーが、ナノ粒子表面上で発現され、これは、アプタマーのmgあたりアプタマーの約100マイクログラムに言い換えられる。
この実施例では、良好に特徴付けられたナノ粒子処方物が、診療所における使用に適切な物理化学的性質、薬物放出動力学および安定性特徴とともに示される。ここで、化学療法薬物カプセル化生分解性ナノ粒子が示される。標的化されたナノ粒子の組成物は、以下の4つの成分から作製されている:ポリ(乳酸−コ−グリコール酸)(PLGA)、FDA認可制御放出ポリマーシステム、これは、薬物をカプセル化し、そしてそれを経済的に放出する(薬物拡散およびポリマー分解の両方によって仲介され得る性質である);ポリ(エチレングリコール)(PEG)、ナノ粒子の循環半減期を増加し得るFDA認可ポリマー;薬物ドセタキセル(Dtxl)、臨床実践で広く使用されているFDA認可化学療法剤;および前立腺特異的膜抗原(PSMA)に高親和性および特異性で結合し得、PCa細胞の表面上および多くの腫瘍微小血管系上で顕著に上方制御され、そして細胞表面から基礎速度でリサイクルされ、標的細胞中へのナノ粒子−アプタマー生体結合物の摂取を可能にする、56塩基対のA10 2’−フルオロピリミジン、ヌクレアーゼ安定化RNAアプタマー(アプタマーと称される)。
この実施例は、PEG化アプタマー−ナノ粒子生体結合体のLNCaP細胞への結合が、A10アプタマーを欠くコントロールペグ化ナノ粒子と比較したとき、顕著に増大されたことを示す(図7)。標的化されたナノ粒子は、アプタマーの3ブロックコポリマーを、異なる量のPLGA−PEGの2ブロックコポリマーと混合することにより処方された(図4A)。ナノ粒子は、14C−放射標識されたパクリタキセルとともに同時カプセル化された。PCa細胞により食作用されたナノ粒子の%は、これら細胞中で検出された14Cの放射活性の量によって定量された。PSMAタンパク質を発現しないPC3前立腺上皮細胞の場合には、結合における測定可能な差異は、生体結合体とコントロール群との間では観察されなかった(図11)。
この実施例は、マウスにおけるLNCap腫瘍細胞をインビボで標的化することを示す。ヒト異種移植片前立腺腫瘍を、8週齢balb/cヌードマウス(Charles River Laboratories、Wilmington、MA、USA)中に誘導した。マウスに、右横腹に、培地およびマトリゲル(BD Biosciences、Franklin Lakes、NJ、USA)の1:1混合物中に懸濁された4百万LNCap細胞を皮下注射した。腫瘍誘導における使用の前に、LNCap細胞は、10%の胎児ウシ血清、100単位/mLのペニシリンG、および100mg/mLのストレプトマイシンで補填したRPMI−1640培地中で培養した。腫瘍標的化研究は、マウスが100mgの腫瘍を発症した後に実施された。20匹のマウスを、4つの群にランダムに分けた(5%アプタマー3ブロックナノ粒子、2%アプタマー3ブロックナノ粒子、5%非官能化DHA3ブロック、3ブロックなしのナノ粒子)。腫瘍内注入のため、マウスをアベチンの腹腔内注射(200mg/kg体重)により麻酔し、そして腫瘍内に異なるナノ粒子処方物を投薬した。全身投与のためには、ナノ粒子は、後眼窩注射によって投与された。これらナノ粒子は、投与の前に、14C−パクリタキセルをカプセル化することによりトレースされた。異なる群は、24時間に安楽死され、そして200mLの血液が各マウスから心臓穿刺によって引き抜かれた。腫瘍、心臓、肺、肝臓、脾臓および腎臓が、各動物から回収された。組織の14C含量は、Packard Tri−Carb Scintillation Analyser(Downers Grove、IL、USA)中でアッセイされた。これら組織は、Solvable(Packard)中で可溶化され、そして活性は、Hionic−Fluorシンチレーションカクテル(PerkinElmer、Boston、MA、USA)中でカウントされた。各マウスからの肝臓は、その大きなサイズ故ホモゲナイズされ、そして100mgの組織が、分析のためにシンチレーションバイアル中に配置された。その他の器官は、シンチレーションバイアル中に直接配置された。各器官を、2mL溶媒中で12時間60℃で可溶化し、そして得られる溶液を200mLの過酸化水素で1時間60℃で脱色した。血液については、400mLのSolvableを添加し、そしてバイアルは、そうでなければ、上記組織と同様に処理された。100%用量を決定するために、処方されたナノ粒子のバイアルは、上記組織に沿ってカウントされた。データは、組織のグラムあたり注射された用量の%として呈示される。
Claims (22)
- 粒子の集団を含むナノ粒子組成物であって:
該粒子の集団は、1マイクロメーターより小さい平均特徴寸法を有する粒子を含み、
該集団の各々の粒子が、両親媒性マクロ分子を含み、
該マクロ分子は、
第1の疎水性部分、
第2の親水性部分、および
標的化成分または抗原性成分を含む第3の部分を含み、
ここで、該第1の疎水性部分、該第2の親水性部分またはその両方が、生体適合性ポリマーを含み、該粒子は、該ナノ粒子の表面に該第3の部分の成分を指向させる自己アセンブリプロセスによって形成され、ここで、該粒子の内側の成分が検出可能な量で存在し、該集団の各々の粒子は、該マクロ分子を含む溶液を提供する工程、および、該溶液をポリマー非溶媒と接触させる工程であって、該マクロ分子は、自己アセンブリして、該第2の親水性部分の実質的に全てを外側に有し、そして該第1の疎水性部分の実質的に全てを内側に有する該粒子を生成する、工程を包含するプロセスによって作製される、ナノ粒子組成物。 - 前記ポリマーが、ブロックコポリマーである、請求項1に記載の組成物。
- 前記ポリマーが、両親媒性である、請求項1に記載の組成物。
- 前記マクロ分子の少なくとも一部分が、生分解性である、請求項1に記載の組成物。
- 前記生体適合性ポリマーが、ポリ(ラクチド−コ−グリコリド)、ポリ(ラクチド)、ポリ(グリコリド)、ポリ(オルトエステル)、ポリ(カプロラクトン)、ポリリジン、ポリ(エチレンイミド)、ポリ(アクリル酸)、ポリ(ウレタン)、ポリ(酸無水物)、ポリ(エステル)、ポリ(トリメチレンカーボネート)、ポリ(エチレンイミン)、ポリ(βアミノエステル)、およびこれらのコポリマーからなる群より選択されるポリマーを含む、請求項1に記載の組成物。
- 前記標的化成分が、ポリペプチド、核酸、脂肪酸、炭水化物、ペプチドグリカン、および糖ペプチドからなる群より選択される分子を含み、該標的化成分は、前記ポリマーに結合される、請求項1に記載の組成物。
- 前記標的化成分が、前立腺特異的膜抗原に特異的に結合する、請求項1に記載の組成物。
- 前記標的化成分が、抗体もしくは抗原、または抗体フラグメントもしくは抗原フラグメントを含む、請求項1に記載の組成物。
- 前記標的化成分が、細胞表面の分子に特異的に結合し得る、請求項1に記載の組成物。
- 前記集団の各々の粒子が、前記標的化成分または前記抗原性成分を含まない生体適合性ポリマーを含む第2のマクロ分子をさらに含む、請求項1に記載の組成物。
- 前記集団の各々の粒子が、薬物をさらに含む、請求項1に記載の組成物。
- 前記薬物が、疎水性であり、そして前記粒子中の前記ポリマーの疎水性部分と会合している、請求項11に記載の組成物。
- 前記集団の各々の粒子が、ドセタキセルを含む、請求項1に記載の組成物。
- 前記集団の各々の粒子が、150nmより小さい平均特徴寸法を有する、請求項1に記載の組成物。
- 前記ブロックコポリマーが、ポリ(アルキレングリコール)を含む第3のブロックをさらに含む、請求項2に記載の組成物。
- 前記マクロ分子を含む溶液が有機溶液であり、そして前記ポリマー非溶媒が水溶液である、請求項1に記載の組成物。
- 請求項1に記載のナノ粒子組成物であって:
前記集団の各々の粒子は、第1のマクロ分子および第2のマクロ分子を含み;
ここで、該第1のマクロ分子が、第1の生体適合性ポリマー、ポリ(アルキレングリコール)、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含むブロックコポリマーであり;
そしてここで、該第2のマクロ分子が、ポリ(アルキレングリコール)および該第1の生体適合性ポリマーから区別可能な第2の生体適合性ポリマーを含むブロックコポリマーである、組成物。 - 請求項1に記載のナノ粒子組成物であって:
前記集団の各々の粒子は、第1のマクロ分子および第2のマクロ分子を含む表面を有する粒子を含み、該第1のマクロ分子が、第1の長さを有する第1のポリ(アルキレングリコール)鎖、および標的化成分、造影成分、キレート成分、複数荷電基を有する成分、および治療成分からなる群から選択される成分を含み、そして該第2のマクロ分子が、該第1の長さとは異なる第2長さを有するポリ(アルキレングリコール)鎖を含む、ナノ粒子組成物。 - 前記マクロ分子の少なくとも一部は、加水分解可能である、請求項4に記載の組成物。
- 前記標的化成分は、細菌膜タンパク質、サイトカイン、ケモカイン、増殖因子、インスリン、エリスロポイエチン、腫瘍壊死因子、糖タンパク質、接着分子、フィブロネクチン、ラミニンおよび抗原からなる群より選択される生物的実体に特異的に結合することができる、請求項1に記載の組成物。
- 前記ナノ粒子は、抗原を含む、請求項1に記載の組成物。
- 前記ポリ(アルキレングリコール)は、ポリ(エチレングリコール)を含む、請求項15に記載の組成物。
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PCT/US2007/011748 WO2007133807A2 (en) | 2006-05-15 | 2007-05-15 | Polymers for functional particles |
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